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PTEN function: the long and the short of it
Open accessAbstract
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a phosphatase that is frequently altered in cancer. PTEN has phosphatase-dependent and -independent roles, and genetic alterations in PTEN lead to deregulation of protein synthesis, the cell cycle, migration, growth, DNA repair, and survival signaling. PTEN localization, stability, conformation, and phosphatase activity are controlled by an array of protein-protein interactions and post-translational modifications. Thus, PTEN-interacting and -modifying proteins have profound effects on the tumor suppressive functions of PTEN. Moreover, recent studies identified mechanisms by which PTEN can exit cells, via either exosomal export or secretion, and act on neighboring cells. This review focuses on modes of PTEN protein regulation and ways in which perturbations in this regulation may lead to disease.
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“A tumour suppressor gene, like phosphatase and tensin homologue (PTEN), is commonly mutated in wide ranges of GBM, which may be a great candidate for therapeutic intervention27,54.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [54]
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The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
Melanoma genome sequencing reveals frequent PREX2 mutations
Berger, M. F., Hodis, E., Heffernan, T. P., Deribe, Y. L., Lawrence, M. S., Protopopov, A., Ivanova, E., Watson, I. R., Nickerson, E., Ghosh, P., et al. (2012) · Nature · doi:10.1038/nature11071 · Cited by 756
Ubiquitination regulates PTEN nuclear import and tumor suppression
Trotman, L. C., Wang, X., Alimonti, A., Chen, Z., Teruya-Feldstein, J., Yang, H., Pavletich, N. P., Carver, B. S., Cordon-Cardo, C., Erdjument-Bromage, H., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.040 · Cited by 748
SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis
Ikeda, F., Deribe, Y. L., Skånland, S. S., Stieglitz, B., Grabbe, C., Franz-Wachtel, M., van Wijk, S. J. L., Goswami, P., Nagy, V., Terzic, J., et al. (2011) · Nature · doi:10.1038/nature09814 · Cited by 745
MC1R Is a Potent Regulator of PTEN after UV Exposure in Melanocytes
Cao, J., Wan, L., Hacker, E., Dai, X., Lenna, S., Jimenez-Cervantes, C., Wang, Y., Leslie, N. R., Xu, G. X., Widlund, H. R., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.010 · Cited by 144
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Self-citation
Metadata
- Authors
- Hopkins, B. D., Hodakoski, C., Barrows, D., Mense, S. M., & Parsons, R. E.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Parsons, Ramon E.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 39
- Issue
- 4
- Pages
- 183-190
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC4043120
- OpenAlex
- W2109559424
- Cited by
- 309
- References
- 125
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 29 · 2023: 21 · 2022: 24 · 2021: 35 · 2020: 36 · 2019: 32 · 2018: 22 · 2017: 22 · 2016: 13 · 2015: 25 · 2014: 11
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA097403, R01CA082783, R01CA155117, R01CA184016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- PTEN, phosphatase and tensin homolog, tumor suppressor, phosphatase activity, protein-protein interaction, post-translational modification, protein stability, cancer, cell cycle regulation, DNA repair, cell migration
- MeSH terms
- Animals, Cell Cycle, Gene Expression Regulation, Humans, Protein Processing, Post-Translational, Genomic Instability, PTEN Phosphohydrolase
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